# Genomic analysis of a prevalent canine peripheral neuropathy > **NIH NIH R03** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $114,750 ## Abstract Project Summary and Abstract Peripheral neuropathies are an important health problem for the American population. While peripheral neuropathies are commonly caused by diabetes and chemotherapy agents, a genetic-neuropathy, Charcot- Marie-Tooth disease (CMT), is the most common inherited neurologic disorder in people. CMT affects about 1 in 2,500 people in the USA. Currently, there is no disease-modifying treatment for any CMT subtype. CMT is associated with mutations in genes that encode proteins involved in a variety of functions linked with myelination and axonal physiology. These mutations ultimately lead to impaired motor and sensory nerve function. Over 80 genes have been associated with CMT, although >30% of CMT patients do not have a genetic diagnosis. The most common forms of CMT are inherited in an autosomal dominant fashion. Dogs are also affected by a variety of peripheral neuropathies, which are generally breed-related, indicating a substantial genetic component. Late-onset peripheral neuropathy (LPN) is a common inherited condition that is prevalent in the Labrador Retriever breed. Our long-term goal is to develop an effective disease-modifying treatment for human peripheral neuropathy through testing drug candidates in the LPN canine model. Therefore, the objective of this application is to discover LPN candidate variant(s) in the Labrador Retriever. Many pathologic features of Labrador LPN are shared with human peripheral neuropathy. Our data suggest that LPN is an autosomal dominant trait in the Labrador Retriever. The central hypothesis of this application is that canine LPN is the result of a large structural variant. To accomplish the objective of this application we will pursue the following specific aims: 1) Discover structural genomic variants in LPN candidate loci in the Labrador Retriever and 2) Identify transcriptome alterations in neuronal cell bodies and axons of LPN- affected Labrador Retrievers. We will create a guided assembly of the Labrador Retriever genome, which will be a valuable reference for the next-generation sequencing studies proposed. We will perform long-range whole genome sequencing to identify a disease-associated structural variant. Finally, neuronal tissue, obtained from LPN cases and controls, will be studied using RNA-sequencing to identify differentially expressed genes or enriched signaling pathways in diseased tissue. The research proposed is innovative because it uses a battery of current technologies to investigate the genetic basis of a naturally occurring canine neuropathic disease, taking into consideration breed-associated genomic structure. This work is expected to discover a strong candidate LPN genetic variant. Such a result will enable development of a canine model for human peripheral neuropathy and enhance our trajectory towards development of a strong independent R01 application that will propose to confirm the candidate variant as causal and advance investigation of LPN neuropatho... ## Key facts - **NIH application ID:** 9989927 - **Project number:** 5R03OD026601-02 - **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON - **Principal Investigator:** Susannah Sample - **Activity code:** R03 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2020 - **Award amount:** $114,750 - **Award type:** 5 - **Project period:** 2019-08-15 → 2023-01-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/9989927 ## Citation > US National Institutes of Health, RePORTER application 9989927, Genomic analysis of a prevalent canine peripheral neuropathy (5R03OD026601-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9989927. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*